Rationally designed foldameric adjuvants enhance antibiotic efficacy via promoting membrane hyperpolarization.
Rationally designed foldameric adjuvants enhance antibiotic efficacy via promoting membrane hyperpolarization.
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DOI：
10.1039/d1me00118c
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发表时间：
2022-01-04
影响因子：
3.6
通讯作者：
Martinek TA
中科院分区：
文献类型：
--
作者：
Bhaumik KN;Hetényi A;Olajos G;Martins A;Spohn R;Németh L;Jojart B;Szili P;Dunai A;Jangir PK;Daruka L;Földesi I;Kata D;Pál C;Martinek TA
细菌细胞的负膜电位影响关键的细胞过程。受抗菌肽PGLa分子支架的启发，我们开发了具有计算机指导设计策略的抗菌文件夹。新型PGLa类似物诱导持续的膜超极化。当作为佐剂共同给药时，所产生的化合物PGLb1和PGLb2大大降低了多重耐药大肠杆菌、肺炎克雷伯菌和福氏志贺氏菌临床分离株的抗生素耐药性水平。观察到的抗生素增强作用是由细胞离子转运改变引起的细菌膜的超极化介导的。具体来说，PGLb1和PGLb2是选择性离子载体，可增强细菌膜上的戈德曼-霍奇金-卡茨电位。这些发现表明，操纵细菌膜电生理可能是克服抗菌素耐药性的有价值的工具。抗菌文件夹降低多重耐药革兰氏阴性细菌的抗生素耐药性。它们作为选择性离子载体，在低浓度下使膜超极化，增强膜上的ghk电位。
The negative membrane potential of bacterial cells influences crucial cellular processes. Inspired by the molecular scaffold of the antimicrobial peptide PGLa, we have developed antimicrobial foldamers with a computer-guided design strategy. The novel PGLa analogues induce sustained membrane hyperpolarization. When co-administered as an adjuvant, the resulting compounds – PGLb1 and PGLb2 – have substantially reduced the level of antibiotic resistance of multi-drug resistant Escherichia coli, Klebsiella pneumoniae and Shigella flexneri clinical isolates. The observed antibiotic potentiation was mediated by hyperpolarization of the bacterial membrane caused by the alteration of cellular ion transport. Specifically, PGLb1 and PGLb2 are selective ionophores that enhance the Goldman–Hodgkin–Katz potential across the bacterial membrane. These findings indicate that manipulating bacterial membrane electrophysiology could be a valuable tool to overcome antimicrobial resistance. Antimicrobial foldamers reduce the antibiotic resistance in multi-drug resistant Gram-negative bacteria. They hyperpolarize the membrane at low concentrations by acting as selective ionophores, enhancing the GHK-potential across the membrane.
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影响因子：
3.7
作者：
AlRabiah H;Allwood JW;Correa E;Xu Y;Goodacre R
通讯作者：
Goodacre R
影响因子：
--
作者：
Johnson, Lisa M.;Gellman, Samuel H.
通讯作者：
Gellman, Samuel H.
影响因子：
4.8
作者：
Bartek IL;Reichlen MJ;Honaker RW;Leistikow RL;Clambey ET;Scobey MS;Hinds AB;Born SE;Covey CR;Schurr MJ;Lenaerts AJ;Voskuil MI
通讯作者：
Voskuil MI
影响因子：
--
作者：
Farha, Maya A.;Verschoor, Chris P.;Brown, Eric D.
通讯作者：
Brown, Eric D.
影响因子：
3
作者：
Duan, Y;Wu, C;Kollman, P
通讯作者：
Kollman, P